Counterfeit medicines pose a global threat to public health; both developing and industrialized countries are exposed to pharmaceutical forgery. These products are not subjected to quality control and therefore their safety, efficacy and quality cannot be guaranteed. The types of medicines which are sold most as counterfeits in industrialized countries are commonly referred to as ‘life style drugs’ and comprise PDE-5 Inhibitors for the treatment of erectile dysfunction and weight loss products. High amounts of counterfeit pharmaceuticals enter the European market. Consequently, analytical techniques able to detect these kind of products and distinguish them from genuine medicines are indispensable. Part II of this dissertation describes all research performed on PDE-5 Inhibitors. Both physical and chemical properties of these samples were taken into consideration to discriminate counterfeit medicines from genuine ones. Chapter V focuses on physical profiling and IR spectroscopy to obtain a prime discrimination between genuine and counterfeit Viagra® and Cialis® medicines. Hypothesis testing showed that most illegal samples differ significantly from genuine medicines, in particular for mass and long length of tablets. CART resulted in a good distinction between genuine and illegal medicines (98.93% correct classification rate for Viagra® and 99.42% for Cialis®). Moreover, CART confirmed that mass and long length are the key physical characteristics which determine the observed discrimination. IR analysis was performed on tablets without blister and on tablets in an intact blister. A perfect discrimination between genuine and counterfeit medicines can be obtained by SIMCA and PLS-DA without the need to remove the tablets from the blister, thereby keeping the blister intact. Chapter VI explores the usage of ATR-FTIR spectroscopy for the screening of counterfeit medicines. ATR-FTIR spectroscopy has the advantages of being easy to use and little sample preparation is required. When combining ATR-FTIR spectroscopy and chemometrics, a suitable diagnostic model was acquired by SIMCA which is able to discriminate between genuine and counterfeit medicines and to distinguish between counterfeit medicines containing a different API. This shows that chemometric analysis of ATR-FTIR fingerprints is a valuable tool to discriminate genuine from counterfeit samples and to classify counterfeit medicines. The potential use of chromatographic fingerprinting is investigated in Chapter VII. In this chapter a HPLC-PDA and HPLC-MS method were developed to acquire impurity fingerprints for a Viagra® and a Cialis® sample set. These fingerprints were included in the chemometric data analysis, aiming to test whether PDA and MS are complementary detection techniques. This extensive data analysis has shown that combining the fingerprints acquired by both types of detection is preferred due to less classification errors. For the Viagra® data set the combination of the MS1 fingerprints and the fingerprints acquired by 254 nm resulted in the best diagnostic models which discriminate between genuine, generic and counterfeit medicines. For the Cialis® sample set, conclusions are more complicated. For both PDA and MS fingerprints separately, perfect models were obtained supporting differentiation between genuine and counterfeit samples. However, the tested sample set is rather small. Therefore, when using a larger sample set including more possible sources of variation, more sophisticated detection techniques such as MS might be necessary. Chapter VIII describes the use of headspace-GC-MS impurity fingerprinting as a means to differentiate genuine from counterfeit medicines. This study shows that a perfect discrimination between genuine and counterfeit pharmaceuticals could be obtained using SIMCA. Furthermore, distinct groups of counterfeits could be defined based on the potential health hazards these products pose. Part III describes all testing performed on the available slimming aid samples. In Chapter IX chromatographic fingerprinting, using PDA and MS detection, was combined with chemometric data analysis. This data analysis showed that suitable diagnostic models can be obtained discriminating between samples containing different APIs. Furthermore, it was shown that MS is preferred over PDA; when using MS as detection technique two types of data sets could be acquired using a single analytical run for each sample. Besides the classical chromatographic fingerprints, MS fingerprints were obtained as well. These MS fingerprints are able to generate more accurate models since even very low concentrations of API could be detected while these particular samples are classified as placebo based on other types of fingerprints. Illegal slimming aids do not only pose a threat to a patient’s health due to adulteration but also due to the presence of potentially toxic plants. A strategy to screen for these kind of plants is explored in Chapter X. Chromatographic fingerprinting has been shown to be useful to screen herbal preparations for the presence of forbidden or regulated plants. The disadvantage of this approach is that a reference standard of the targeted plants needs to be available and the development of a suitable analytical method can be quite time-consuming. However, once the method is developed, herbal samples can be screened for the targeted plants in an efficient way. In general, it can be concluded that fingerprinting proves to be a useful strategy for the screening of counterfeit medicines and adulterated products. Based on the desired information, a suitable analytical technique can be selected. In the future, this working strategy could potentially be expanded to other pharmacological classes of counterfeit medicines such as sleeping aids and pain killers.
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